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CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain.

Abstract
In light of the adverse side-effects of opioids, cannabinoid receptor agonists may provide an effective alternative for the treatment of cancer pain. This study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain. Intraplantar injection of the CB1 receptor agonist arachidonylcyclopropylamide (ED(50) of 18.4 μg) reduced tumor-related mechanical hyperalgesia by activation of peripheral CB1 but not CB2 receptors. Similar injection of the CB2 receptor agonist AM1241 (ED50 of 19.5 μg) reduced mechanical hyperalgesia by activation of peripheral CB2 but not CB1 receptors. Both agonists had an efficacy comparable with that of morphine (intraplantar), but their analgesic effects were independent of opioid receptors. Isobolographic analysis of the coinjection of arachidonylcyclopropylamide and AM1241 determined that the CB1 and CB2 receptor agonists interacted synergistically to reduce mechanical hyperalgesia in the tumor-bearing paw. These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.
AuthorsIryna A Khasabova, James Gielissen, Anisha Chandiramani, Catherine Harding-Rose, Desiree Abu Odeh, Donald A Simone, Virginia S Seybold
JournalBehavioural pharmacology (Behav Pharmacol) Vol. 22 Issue 5-6 Pg. 607-16 (Sep 2011) ISSN: 1473-5849 [Electronic] England
PMID21610490 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • AM 1241
  • Analgesics
  • Arachidonic Acids
  • Cannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • arachidonylcyclopropylamide
  • Morphine
Topics
  • Analgesics (pharmacology)
  • Animals
  • Arachidonic Acids (pharmacology)
  • Cannabinoids (pharmacology)
  • Disease Models, Animal
  • Drug Synergism
  • Hyperalgesia (drug therapy, etiology)
  • Male
  • Mice
  • Mice, Inbred C3H
  • Morphine (pharmacology)
  • Neoplasms, Experimental (complications)
  • Pain (drug therapy, etiology)
  • Receptor, Cannabinoid, CB1 (agonists)
  • Receptor, Cannabinoid, CB2 (agonists)

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